In U.S. Pat. No. 4,943,574 there are described 1H-azol-1 -ylmethyl substituted benzotriazole derivatives which are potent aromatase inhibitors. These compounds are useful in treating estrogen hormone dependent disorders in mammals. 6-[(4-chlorophenyl) (1H-1,2,4-triazol-1-yl)methyl]-1-methyl]1H-benzotriazole in particular is a highly potent and selective inhibitor of the human aromatase. Most of its activity and selectivity, however, originates from its dextrorotatory (S)-enantiomer. Resolution of the racemic benzotriazole compound by selective crystallization of its diastereomeric salts proved impractical.
The present invention is concerned with a process for separating the enantiomers of a hydrazinc intermediate. Said separation is obtained by the selective crystallization of the diastereomeric salts of said intermediate with chiral acids or by chromatographically separating diastereomeric covalent compounds derived from said hydrazine derivative and a chiral acid. The enantiomerically pure intermediate then is further converted into the desired dextrorotatory (S)-benzotriazole end product.